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Cardiopathic effect of 1,2,3‐trichloropropane after subacute and subchronic exposure in rats
Author(s) -
Merrick B. Alex,
Robinson Merrel,
Condie Lyman W.
Publication year - 1991
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.2550110305
Subject(s) - corn oil , toxicity , histopathology , kidney , body weight , atrophy , medicine , physiology , endocrinology , chemistry , toxicology , biology , pathology
1,2,3‐Trichloropropane (1,2,3‐TCP) is an industrial water contaminant with potential for human exposure by the oral route. The systemic toxicology of 1,2,3‐TCP was evaluated after subacute or subchronic exposure in male and female Sprague‐Dawley rats. Animals were treated with 0.01, 0.05, 0.20 and 0.80 mmol kg −1 day −1 for 10 days and 0.01, 0.05, 0.10 and 0.40 mmol kg −1 day −1 for 90 days. Chemical exposure was by oral gavage in corn oil. Lethality did not occur in either study. Toxicity was observed primarily in the high dose group of subacute and subchronically treated rats of both sexes. Weight gain suppression occurred at a dose of 0.8 mmol kg −1 (118 mg kg −1 ) after 10 days. After 90 days of exposure to 0.40 mmol kg −1 , the final body weights were 81% and 86% of control values for males and females, respectively. When major organ weights were normalized by body weight, liver and kidney values were generally increased relative to control in the two highest dose groups after 10‐ and 90‐day chemical exposure. Serum chemistries and histopathology indicated a mild hepatotoxic response to 1,2,3‐TCP in the high dose group of each study but did not support any renal toxicity. Thymic weight reduction due to atrophy occurred at 10 days of exposure in high dose groups but was normal in all groups after the 90‐day treatment. The primary histological finding in this study was an inflammation‐associated cardiopathy produced by 1,2,3‐TCP. Myocardial necrosis and degeneration occurred in a diffuse pattern with marked eosinophilia of affected cells. Male and female animals showed a cardiopathic response only at a dose of 0.8 mmol kg −1 1,2,3‐TCP after the 10‐day exposure. In the subchronic study, the incidence of cardiopathy was more prevalent in males than in females. In addition to cardiac effects, the 90‐day chemical exposure produced bile duct hyperplasia in 40% and 80% of males and females, respectively. This observation may be significant, since five other neoplastic and proliferative lesions were observed in rats receiving 1,2,3‐TCP subchronically. Thus, this study demonstrates that heart and liver were target organs for 1,2,3‐TCP toxicity and suggests that 1,2,3‐TCP exposure may be involved in carcinogenesis.